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Research at Mass General
Mario L. Suvà, M.D., Ph.D
Assistant Professor of Pathology, Harvard Medical SchoolAssistant Molecular Pathologist, Massachusetts General Hospital
Associate Member, Broad Institute of MIT and HarvardCo-Director, Cancer Program, Harvard Stem Cell Institute
Molecular Pathology UnitMassachusetts General Hospital149 13th Street, 6th FloorCharlestown, MA 02129Phone: 617-726-6247
Our laboratory is focused on the biology of brain tumors, in particular diffuse gliomas in adults and children. We study primary human samples at single-cell resolution using transcriptomic and genomic approaches. We reconstruct the cellular composition of patient tumors and relate it to genetic mutations. We model how brain cancer cells exploit developmental programs to establish distinct cellular states. Additionally, the laboratory investigates how genetic events affecting genes involved in chromatin regulation rewire cancer cells’ identities to contribute to cellular transformation. We seek to identify common programs that would offer novel therapeutic options in these dismal diseases.
Heterogeneity in brain tumors assessed at single-cell level
We are deploying cutting-edge single-cell genomic and transcriptional profiling to clinical samples. Our unique approach allows us for the first time to relate genotype to phenotype at single-cell resolution in clinical tumor specimens. Through our efforts, we are redefining our understanding of malignant cell subpopulations in glioblastoma, oligodendroglioma, astrocytoma, diffuse intrinsic pontine glioma, medulloblastoma and synovial sarcoma. In addition, our single-cell genomics efforts are providing invaluable insights into myeloid cells and T cell programs in clinical tumors.
Mariella Filbin, MD, PhD FellowMcKenzie Shaw, Research Technician IIChristine Hebert, Research Technician IICyril Neftel, MD, PhD studentKristof Egervari, MD Visiting Fellow
Single-cell RNA-seq highlights intratumoral heterogeneity in primary glioblastoma. Patel AP, Tirosh I, Trombetta JJ, Shalek AK, Gillespie SM, Wakimoto H, Cahill DP, Nahed BV, Curry WT, Martuza RL, Louis DN, Rozenblatt-Rosen O, Suvà ML, Regev A, Bernstein BE. Science. 2014 Jun 20;344(6190):1396-401.
Filbin MG, Tirosh I, Hovestadt V, Shaw ML, Escalante LE, Mathewson ND, Neftel C, Frank N, Pelton K, Hebert CM, Haberler C, Yizhak K, Gojo J, Egervari K, Mount C, van Galen P, Bonal D, Nguyen QD, Beck A, Sinai C, Czech T, Dorfer C, Goumnerova L, Lavarino C, Carcaboso AM, Mora J, Mylvaganam R, Luo CC, Peyrl A, Popović M, Azizi A, Batchelor TT, Frosch MP, Martinez-Lage M, Ki- eran MW, Bandopadhayay P, Beroukhim R, Fritsch G, Getz G, Rozenblatt-Rosen O, Wucherpfennig KW, Louis DN, Monje M, Slavc I, Ligon KL, Golub TR, Regev A, Bernstein BE, Suvà ML. Devel- opmental and oncogenic programs in H3K27M gliomas dissected by single- cell RNA-seq. Science, 2018.
Venteicher AS, Tirosh I, Hebert C, Yizhak K, Neftel C, Filbin MG,Hovestadt V, Escalante LE, Shaw ML, Rodman C, Gillespie SM, Dionne D, Luo CC, Ravichandran H, Mylvaganam R, Mount C, Onozato ML, Nahed BV, Wakimoto H, Curry WT, Iafrate AJ, Rivera MN, Frosch MP, Golub TR, Brastianos PK, Getz G, Patel AP, Monje M, Cahill DP, Rozenblatt-Rosen O, Louis DN, Bernstein BE, Regev A, Suvà ML. Decoupling genetics, lineages and micro-environment in IDH-mutant gliomas by single-cell RNA-seq. Science. 2017; 55(6332).
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